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Showing papers in "The International Journal of Mycobacteriology in 2019"


Journal ArticleDOI
TL;DR: It is likely that mycobacteriosis incidence will keep escalating and new measures should be taken to deal with these diseases, including their reportability and the implementation of strain genotyping that would shed light on the NTM dissemination routes from the environment or human hosts.
Abstract: Epidemiological data show a worldwide increase in nontuberculous mycobacteriosis. Although it has been partially attributed to the improvement of microbiological methodologies that has allowed a better recovery and identification of nontuberculous mycobacteria (NTM), it is generally accepted that there is a genuine incidence augmentation. The reasons of the increase are likely multifactorial, depending on the nature of the pathogen, the host, and their interaction. Mycobacteria from the Mycobacterium tuberculosis complex has been regarded as pathogenic and NTM as opportunistic and nontransmissible. Nevertheless, few differences have been found in either their phenotypic or genotypic characteristics. The phenomenon of M. tuberculosis adaptation to the human host may be taking place again in NTM as a consequence of human environmental alterations that facilitate the interaction with the pathogen. The current worsening of the immunological status of increasing numbers of individuals, a result of factors such as malnutrition (obesity and diabetes), population aging or the widespread use of immunosuppressive medication, may be allowing the rapid evolution and person-to-person transmission of NTM. It is likely that mycobacteriosis incidence will keep escalating. New measures should be taken to deal with these diseases, including their reportability and the implementation of strain genotyping that would shed light on the NTM dissemination routes from the environment or human hosts.

41 citations


Journal ArticleDOI
TL;DR: The performance of Xpert MTB/RIF assay was comparable to the gold standard culture method for identification of MTB in nonrespiratory clinical specimens, and helps to achieve better sensitivity and obtain rapid results within 2 h.
Abstract: Background: The objective of this study is to assess the performance of Xpert Mycobacterium tuberculosis (MTB)/rifampin (RIF), an automated molecular test for MTB and resistance to RIF, against smear microscopy and culture method for the diagnosis of MTB infection. Methods: This is a retrospective analysis of 168 nonrespiratory patient specimens suspected of tuberculosis (TB) at TB Laboratory of Dubai Health Authority in the United Arab Emirates between September 2016 and November 2018. Each sample underwent smear microscopy, mycobacterial culture, and GeneXpert MTB/RIF test. Results: Of 168 nonrespiratory samples, 52 samples were positive by both culture and Xpert MTB/RIF, 9 samples were detected positive only by culture. Sensitivity, specificity, positive predictive value, and negative value of the Xpert MTB/RIF test were 82.69%, 100%, 100%, and 92.80%, respectively. No false positive was yielded by the Xpert MTB/RIF, and all 116 samples were true negative by Xpert MTB/RIF. The sensitivity of the Xpert MTB/RIF was 76.92% in lymph node tissue and aspirates, 66.67% in cerebrospinal fluid, 100% in gastric lavage and aspirate, 81.25% in other body fluids, 100% in pus, 85.71% in urine, and 66.67% in other tissue samples. Of 168 strains, five strains were rifampicin resistant by phenotypic and Xpert MTB/RIF and 163 were susceptible to rifampicin with culture and Xpert MTB/RIF. Conclusion: The performance of Xpert MTB/RIF assay was comparable to the gold standard culture method for identification of MTB in nonrespiratory clinical specimens. It does not replace the gold standard culture method, but it helps to achieve better sensitivity and obtain rapid results within 2 h.

25 citations


Journal ArticleDOI
TL;DR: The treatment success rate of overall TB patients is lower than end TB Strategy target of ≥90% success rate, and Smear-negative PTB, EPTB cases, and those with unknown HIV status tend to have unsuccessful outcome.
Abstract: Background: Monitoring the outcome of tuberculosis (TB) treatment and investigating factors associated with unsuccessful outcome are essential, as unsuccessful treatment fuels resistance to antibiotics. This study aimed to investigate the treatment outcome and associated factors with an unsuccessful outcome at Jimma University Medical Center (JUMC), Southwest Ethiopia. Methods: A 5-year retrospective analytical study, including all types of TB cases who sought care at JUMC between September 1, 2012, and August 31, 2017, was conducted. Treatment outcomes and TB types were categorized according to the National TB Control guideline. Bivariate analysis was used to analyze the association between treatment outcome and potential variables. Results: Overall data from 1249 patients' records were included in the study. The proportion of male patients was higher (815, 65.3%) than that of females. The mean age (± standard deviation, range) of the cases was 26 (±11. 6, 1–71) years. Of the total, 292 (23.3%) were smear-positive pulmonary TB (PTB), 489 (39.2%) smear-negative PTB, and 468 (37.5%) extra-PTB (EPTB) cases. Available treatment outcomes indicate that 253 (20.2%) were cured, 850 (68.0%) completed therapy, 58 (4.8%) died, 83 (6.6%) defaulted, and 5 (0.4%) failed the therapy. About 76 (5.6%) cases were transferred out and 44 (3.2%) cases were lost to follow-up. In total, 146 (11.7%) patients had an unsuccessful outcome. Unsuccessful treatment outcome was associated with smear-negative PTB (odds ratio [OR] =2.0, 95% confidence intervals [CI] =1.1, 3.7), EPTB (OR = 2.1, 95% CI = 1.2, 3.4), and unknown human immunodeficiency virus (HIV) status (OR = 7.9, 95% CI = 2.5, 25.0). Conclusion: The treatment success rate of overall TB patients is lower than end TB Strategy target of ≥90% success rate. Smear-negative PTB, EPTB cases, and those with unknown HIV status tend to have unsuccessful outcome.

19 citations


Journal ArticleDOI
TL;DR: Examining novel compounds and approaches to combatting AMR in the nontuberculous mycobacteria, specifically examining antimycobacterial compounds from plants and venoms, as well as examining synergistic and combination effects with other antimicrobials.
Abstract: The nontuberculous mycobacteria (NTM) have recently emerged as important bacterial pathogens of both animals and humans. Of particular, concern is the high level of antimicrobial resistance (AMR) displayed by these organisms, which complicates treatment and potential successful outcomes. This review, therefore, wishes to examine novel compounds and approaches to combatting AMR in the NTMs, specifically examining antimycobacterial (NTM) compounds from plants and venoms, as well as examining synergistic and combination effects with other antimicrobials. Novel and modified drugs including new inhaled drugs are examined, as well as the repurposing of existing drugs for antimycobacterial activity. Many of these novel interventions are at various stages of development, from initial concept through to licensed intervention. The challenge remains to translate these interventions from in vitro laboratory models to effective in vivo interactions. When these are realized, then we will have the opportunity of overcoming NTM AMR, to the benefit of medicine, society, and humanity.

17 citations


Journal ArticleDOI
TL;DR: Smoking and high initial VL were independent risk factors of unsuppressed VL in HIV-1-infected patients on antiretroviral therapy after 6 months of the first-line ART, highlighting the importance of developing and evaluating targeted interventions for patients at risk of un suppressive VL on ART.
Abstract: Background: Nonsuppression of viral load (VL) in HIV-infected patients on antiretroviral therapy (ART) is associated with increased HIV transmission and poor survival. The objective of this work was to evaluate the factors associated with the unsuppressed VL (VL >400 copies/ml) in HIV-1-infected patients after 6 months of the first-line ART. Methods: This was a retrospective cohort study of 181 patients living with HIV-1 on ART in Dermatology and Venereology Department of Mohamed V Military Teaching Hospital of Rabat, during the period between January 1, 2007, and January 1, 2017. Associated factors were identified through a logistic regression model. Results: Of the 181 patients, 76% were men. At inclusion, the median age was 35 years. Five variables (male sex, initial fasting glucose >1.1 g/l, alcoholism, smoking, and initial VL >10,000 copies/ml) were significantly associated (P 10,000 (RR: 9.78, 95% CI: 2.40–39.73) were associated independently with unsuppressed VL. Conclusion: Approximately 83% of the patients in the cohort had been able to suppress VL after 6 months of the first-line ART. Smoking and high initial VL were independent risk factors of unsuppressed VL. This work highlights the importance of developing and evaluating targeted interventions for patients at risk of unsuppressed VL on ART.

16 citations


Journal ArticleDOI
TL;DR: Uncommon variants of ENL can be very commonly misdiagnosed in patients, especially in those who have not been previously diagnosed with leprosy, Hence, a high index of suspicion is required in such cases to avoid delay in the diagnosis and resulting morbidity.
Abstract: Background: Erythema nodosum leprosum (ENL) classically presents with tender, coppery, evanescent nodules along with constitutional features and visceral involvement. However, uncommon morphological variants of ENL-like erythema nodosum necroticans, erythema multiforme (EM)-like ENL, Sweet's syndrome (SS)-like ENL, Lucio phenomenon, and reactive perforating type of ENL have also been described in the literature. The primary objective of this study was to describe the clinical features of the severe and uncommon morphological variants of ENL. Methods: This was an observational case series with retrospective review of records of all ENL patients with ulceronecrotic lesions admitted in the Department of Dermato-venereo-leprology of a tertiary health center of central India over a period of 2 years. Results: Eighteen patients were included, all of whom had ulceronecrotic lesions. Four out of them had EM like ENL, two had SS-like presentation, and one of them had annular bullous lesions over old infiltrated plaques of leprosy. Conclusions: Uncommon variants of ENL can be very commonly misdiagnosed in patients, especially in those who have not been previously diagnosed with leprosy. Hence, a high index of suspicion is required in such cases to avoid delay in the diagnosis and resulting morbidity.

16 citations


Journal ArticleDOI
TL;DR: The results of GeneXpert MTB/RIF to be a fundamental diagnosis of RR-TB and subsequently to notify MDR-TB were satisfying and valuable in this study.
Abstract: Background: Tuberculosis (TB) is the fourth leading cause of death in Indonesia. In 2017, the World Health Organization (WHO) estimated that only 2% of the TB patients in Indonesia had only been tested with rapid diagnostics at the time of diagnosis, resulting in largely underdetected rifampicin-resistant TB (RR-TB). Utilization of GeneXpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) assay as a point-of-care molecular assay to detect TB and RR-TB and serving its purpose in accordance with the first pillar of the WHO End-TB Strategy. Objective: This study investigated the use of GeneXpert MTB/RIF assay to determine the molecular epidemiology of RR-TB in an urban setting of Indonesia. Methods: All molecular epidemiological and microbiological databases were retrospectively examined from GeneXpert MTB/RIF assay results in Siloam Hospital Lippo Village. The sociodemographic characteristics and results of microbiological examinations consisting of Ziehl–Neelsen staining and GeneXpert MTB/RIF assay were analyzed. Results: During the study period, 600 cases were registered, and GeneXpert MTB/RIF tests were done in which the tests yielded 597 (99.5%) valid results; 62.0% were male and adult of age category; of whom 29 samples (4.9%) were found to be RR-TB, 186 samples (31.2%) were RIF sensitive, and remainders were negative. Conclusions: The results of GeneXpert MTB/RIF to be a fundamental diagnosis of RR-TB and subsequently to notify MDR-TB were satisfying and valuable in this study. This further increased and reinforced TB surveillance and national TB program to finally bring about WHO end-TB strategy one step closer in Indonesia.

16 citations


Journal ArticleDOI
TL;DR: In this article, the authors extended the existing scheme from PubMLST using whole-genome data for M. abscessus by extracting data for 15 genetic regions within the M.Abscessus genome.
Abstract: Background:Mycobacterium abscessus is a rapid growing nontuberculous mycobacteria (NTM) and a clinically significant pathogen capable of causing variable infections in humans that are difficult to treat and may require months of therapy/surgical interventions. Like other NTMs, M. abscessus can be associated with outbreaks leading to complex investigations and treatment of affected cases. Typing schemes for bacterial pathogens provide numerous applications; including identifying chain of transmission and tracking genomic evolution, are lacking or limited for many NTMs including M. abscessus. Methods: We extended the existing scheme from PubMLST using whole-genome data for M. abscessus by extracting data for 15 genetic regions within the M. abscessus genome. A total of 168 whole genomes and 11 gene sequences were used to build this scheme (MAB-multilocus sequence typing [MLST]). Results: All seven genes from the PubMLST scheme, namely argH, cya, gnd, murC, pta, purH, and rpoB, were expanded by 10, 14, 13, 10, 13, 10, and 9 alleles, respectively. Another eight novel genes were added including hsp 65, erm(41), arr, rrs, rrl, gyrA, gyrB, and recA with 16, 16, 25, 7, 32, 35, 29, and 15 alleles, respectively, with 85 unique sequence types identified among all isolates. Conclusion: MAB-MLST can provide identification of M. abscessus complex to the subspecies level based on three genes and can provide antimicrobial resistance susceptibility prediction based on results from seven genes. MAB-MLST generated a total of 85 STs, resulting in subtyping of 90 additional isolates that could not be genotyped using PubMLST and yielding results comparable to whole-genome sequencing (WGS). Implementation of a Galaxy-based data analysis tool, MAB-MLST, that simplifies the WGS data and yet maintains a high discriminatory index that can aid in deciphering an outbreak has vast applicability for routine diagnostics.

12 citations


Journal ArticleDOI
TL;DR: The GenoType® MTBDRplus Ver 2.0 assay's sensitivity and specificity show that the assay is highly accurate for the detection of RIF and INH resistance and thus can be used as an alternate platform due to its shorter results turnaround time.
Abstract: Background: Multidrug-resistant tuberculosis (MDR-TB) is a public health concern globally. MDR-TB is defined as resistance to rifampicin (RIF) and isoniazid (INH), the two-major anti-TB first-line TB treatment drugs. Rapid identification of MDR-TB can contribute significantly to the control of TB. The GenoType® MTBDRplus Ver 2.0 assay is a molecular assay used to detect genetic mutations that result in RIF and INH resistance. The aim of this study was to validate the performance of the GenoType® MTBDRplus Ver 2.0 assay for the detection of INH and RIF resistance. Methods: Fifty-five stored Mycobacterium tuberculosis isolates were tested using both the mycobacterial growth indicator tube (MGIT), antimicrobial susceptibility testing (AST), and the GenoType® MTBDRplus Ver 2.0 assay. The MGIT AST was done according to the BBL MGIT AST SIRE system with RIF and INH final critical concentrations of 1.0 μg/ml and 0.1 μg/ml, respectively. The GenoType® MTBDRplus assay (Hain Lifescience, Germany) was performed following the manufacturer's instructions. Results: The GenoType® MTBDRplus Ver 2.0 assay had a sensitivity, specificity, positive predictive value, and negative predictive value of 100% for INH and RIF resistance. The intra-assay precision for the assay was 100%. Conclusion: The GenoType® MTBDRplus Ver 2.0 assay's sensitivity and specificity show that the assay is highly accurate for the detection of RIF and INH resistance and thus can be used as an alternate platform due to its shorter results turnaround time.

12 citations


Journal ArticleDOI
TL;DR: MDR strains were less competitive than WT strains in 83.3% of cases and generation number of WT strains was less than those of MDR strains in both individual and competitive culture.
Abstract: Background: While, bacteria resistance mutations can affect competitive fitness, given our multidrug-resistant (MDR) prevalence, we conducted this study to determine the impact of MDR on the competitive fitness of Mycobacterium tuberculosis (MTB) complex MDR strains. We conducted a cross-sectional study at the University Clinical Research Center (UCRC) from January to December 2017. New TB patients over aged of 18 were recruited at University teaching hospital and health reference centers of Bamako in USTTB Ethical committee approved protocols. Methods: MDR and drug-susceptible (wild-type [WT]) MTB strains (T1 and Beijing) and MTB H37Rv were competed on solid media in UCRC's Tuberculosis Laboratory. Competitive and individual cultures were incubated for 14 days at 37°C with 7% CO2. Number of generation, generation time, and relative competitive fitness (W) of the strains were calculated. Data were analyzed with Epi-Info 7.1.5.2 software (CDC). P value was considered significant when it was

12 citations


Journal ArticleDOI
TL;DR: Oral administration of UDCA to TB patients developing anti-TB drug-induced liver injury may reverse hepatotoxicity in adults.
Abstract: Background: Tuberculosis (TB) remains a global health problem. The application of rifampicin-based regimens for antimycobacterial therapy is hampered by its marked hepatotoxicity which results in poor adherence and may contribute to prolonged therapy or treatment failure. The purpose of this prospective investigation was to evaluate the hepatoprotective effectiveness of oral ursodeoxycholic acid (UDCA) (250–500 mg TID) administered to TB- or non-TB mycobacterial (NTM)-infected patients with drug-induced hepatotoxicity and ongoing therapy. Methods: Study population: During 2009–2017, 27 patients (11 women, 16 men, aged 19–90 years; median age 44 years, 16 Caucasians, 10 Africans, 1 Asian) out of 285 patients with active TB (24/261) or NTM infections (3/24) treated at our TB Center developed clinically relevant hepatotoxicity. Oral UDCA was administered to treat hepatotoxicity. Results: Twenty-one out of 27 patients (77.8%) showed normalization of elevated enzymes (alanine transferase and aspartate aminotransferase), alkaline phosphatase, and bilirubin while continuing TB treatment and 5 patients demonstrated a significant reduction of liver enzymes (18.5%). No change was observed in 1 patient (3.7%). Drug dose was not reduced in all patients; they all showed radiological and clinical improvement. There were no significant side effects. Conclusion: Oral administration of UDCA to TB patients developing anti-TB drug-induced liver injury may reverse hepatotoxicity in adults.

Journal ArticleDOI
TL;DR: This study aims to identify phytochemicals targeting multiple drug targets of Mycobacterium tuberculosis (MTB) through subtractive genomic/proteomic approach followed by in silico screening of phytochemistryicals with reported anti-TB activity.
Abstract: Background: The increasing incidence of multidrug-resistant cases of tuberculosis (TB) and difficulty in treating these cases requires an urgent need to find an effective anti-TB drug. There are many phytochemicals with reported antibacterial and antitubercular activities. Instead of targeting only a single target of Mycobacterium tuberculosis (MTB), this study aims to identify phytochemicals targeting multiple drug targets of MTB through subtractive genomic/proteomic approach followed by in silico screening of phytochemicals with reported anti-TB activity. Methods: Of 614 essential genes of MTB reported in database of essential genes, 15 gene products were selected using different bioinformatic resources and tools such as PANTHER, Venny, NCBI, and BLAST. Results: Virtual screening analysis of these selected drug targets against identified 148 phytochemicals revealed that amentoflavone, carpaine, 13'bromo-tiliacorinine, and 2'nortiliacorinine, able to inhibit more than one target of MTB. Conclusion: These selected compounds may be proposed as potential inhibitors of MTB and need to be tested in TB culture studies in vitro to assess their anti-TB activity.

Journal ArticleDOI
TL;DR: This analysis demonstrated that these dysregulated miRNAs have central roles in the host metabolic and energy pathways, and suggests that the host miRNA network is perturbed by Mycobacterium to re-patterning host metabolism machinery to favor its intracellular survival.
Abstract: Background: Tuberculosis (TB) still remains a major health threat worldwide. The current TB diagnostics are suboptimal, and there is a high clinical need for identifying novel biomarkers of disease prevalence. Circulating exosomes have been currently attractive as novel biomarkers in a wide range of pathological conditions. Methods: In this study, we performed bioinformatics analysis on the downstream targets of a dysregulated microRNA (miRNA) cluster induced by Bacillus Calmette–Guerin infection of human macrophages to provide greater understanding of their potential roles in disease pathogenesis. Results: Our analysis demonstrated that these dysregulated miRNAs have central roles in the host metabolic and energy pathways. Conclusion: This suggests that the host miRNA network is perturbed by Mycobacterium to re-patterning host metabolism machinery to favor its intracellular survival. The dysregulated miRNAs can be delivered to local and distal cells by exosomes and thereby modulate their function.

Journal ArticleDOI
TL;DR: Weight loss, age, alcohol, smoking, and pregnancy were showed to affect the survival probability of TB/HIV patients' coinfection significantly, and the probability of survival in HIV-positive TB patients was significantly lower during the TB treatment.
Abstract: Background: Tuberculosis (TB) with human immunodeficiency virus (HIV) coinfection is the highest clinical epidemiology and public health issue. Despite many programs established to tackle the epidemic, TB target controls have not been reached. One of the many factors attributed to the failure in TB treatment is HIV coinfection. The aim of this study is to assess the survival rate of HIV infection among TB patients and the risk factors of death among the TB patients with HIV coinfection during the retro of directly observed treatment, short-course (DOTS) program. Methods: This study is a retrospective cohort conducted to compare the survivorship between TB/HIV patients for 8 months DOTS. Death among TB patients was considered as failures and those defaulted or survived were censored. The Cox proportional-hazards regression and log-linear model were used to establish the hazard ratio (HR) of death for each variable at baseline and estimate the risk factors effect among TB patients. Results: The findings revealed that 50% of death from TB/HIV patients were from HIV coinfection (advanced HR = 2.01, 95% confidence interval = 1.13–3.17). The risk of death was significantly higher in HIV-positive TB patients (P = 0.000) during the extension care phase. TB/HIV-positive patients on antiretroviral therapy have decreased survival rate (log-rank test = 14.88, df = 2, P = 0.0001). The probability of TB patients surviving is significantly decreased in HIV positive with some factors such as age, weight, smoking, and alcohol found significant. Conclusion: The probability of survival in HIV-positive TB patients was significantly lower during the TB treatment. Weight loss, age, alcohol, smoking, and pregnancy were showed to affect the survival probability of TB/HIV patients' coinfection significantly.

Journal ArticleDOI
TL;DR: It should be taken into account that sequencing of the 16S rRNA gene and biochemical tests are useful for the identification of several species, but it is necessary to incorporate other genes (hsp 65 and rpo B) to obtain accurate identification.
Abstract: Background: There is evidence that tap water is the vehicle through which nontuberculous mycobacteria (NTM) infect or colonize the human body. The objective of this study was to determine the presence and diversity of NTM in the water distribution system of Bahia Blanca city, Argentina (sites S2/S3) and in the dike that supplies water to it (S1). Methods: Culture-dependent method, biochemical tests, and molecular method (16S rRNA sequencing gene) were combined to detect and identify NTM. Results: NTM were isolated in 51.6% (64/124) of all the samples analyzed. Mycobacterium gordonae was the most frequently isolated organism (15/64) in all samples analyzed, followed by Mycobacterium peregrinum and Mycobacterium frederiksbergense. Significant differences were found in the residual chlorine values between sampling S2 and S3. In both sites, maximum counts were recorded but they did not correlate with low chlorine values. A concentration higher than 500 colony-forming unit/L of NTM was never found, which can be attributed to the negative effect caused by decontamination methods being a point to consider for the recovery of NTM. In 46.9% (30/64) of samples, both methods coincided in the identification, and the obtained sequences presented ≥99% identity. Identification at the species level was achieved in 50% (32/64) of the isolates. Nearly 17.2% (11/64) of the isolates showed a similarity

Journal ArticleDOI
TL;DR: An assessment of tuberculosis transmission by genetic methods with the assistance of the standard epidemiologic interview in tuberculosis patients finds that the patients who are in the risk groups may play an important role in the transmission of tuberculosis.
Abstract: Background: The transmission of tuberculosis may affect the incidence rate of the disease in Poland. Genetic methods are of assistance in tracing the infection transmission, identifying its sources, determining the risk groups, and focusing on the preventive actions. Objectives: The objectives of this study lie in an assessment of tuberculosis transmission by genetic methods with the assistance of the standard epidemiologic interview. Methods: The genome DNA of 275 Mycobacterium tuberculosis (Mtb) strains from tuberculosis patients, inhabitants of the city of Krakow, was subjected to a genetic analysis via the spoligotyping method and the IS6110-Mtb1–Mtb2 polymerase chain reaction (PCR) method. If the DNA profiles were identical in both of the PCRs, they were considered identical and classified within one molecular family. Results: Among 275 strains, 104 genetic patterns (spoligotypes) were identified. Two hundred and three strains were divided into 66 molecular families (clusters) and analyzed with the IS6110- Mtb1–Mtb2 PCR method. Eighteen clusters were separated. In the Mtb1–Mtb2 clusters, 21 patients were in the risk groups (the homeless, prisoners, and nursing home residents). We did not confirm any direct or temporary contacts between the patients constituting the Mtb1–Mtb2 clusters (apart from the risk groups). However, the patients in these clusters often lived in the same parts of Krakow. Conclusions: The standard epidemiologic interview in tuberculosis patients should be combined with genetic methods. Active transmission of tuberculosis occurs largely among the individuals maintaining probably periodic contacts. The patients who are in the risk groups may play an important role in the transmission of tuberculosis.

Journal ArticleDOI
TL;DR: Pediatric TB mimics many disorders that primary level centers are not equipped to diagnose or manage, leading to suboptimal outcomes.
Abstract: Background: Children evaluated for tuberculosis (TB) are often diagnosed with miscellaneous conditions that mimic TB. Knowledge of differentials informs policy on service provision through liaison with referral centers offering definitive diagnosis and treatment for common alternative disorders. Methods: We reviewed medical records of children who were offered diagnostic testing for TB (culture or Xpert MTB/RIF) at a tertiary care hospital in Karachi, Pakistan to identify common alternative diagnoses among children who are evaluated for TB. Results: From January 2014 to December 2015, of 126 culture or Xpert MTB/RIF negative children presenting with chronic symptoms, 31 were diagnosed and treated for TB based on clinical criteria (5 of 48 children with pulmonary and 26 of 78 with extrapulmonary presentations; 10.4% and 33.3%, respectively). Among remaining 95 patients, common alternative diagnoses to pulmonary TB (n = 43) were bacterial pneumonia or empyema (60.5%, n = 25) and underlying bronchiectasis (20.9%, n = 9). Among 52 extrapulmonary presentations, the most common alternative diagnoses were lymphoproliferative disorders (n = 11, 21.1%), bacterial infections (n = 11, 21.1%), and autoimmune disorders (n = 9, 17.3%). Of note, five children were diagnosed with underlying primary immunodeficiencies (9.6%). Children with alternative disorders were treated for TB in 25 of 95 cases (26.3%). Although 77.8% (n = 98) children were followed up at the facility, 15.9% (n = 20) were lost to follow-up. Conclusions: Pediatric TB mimics many disorders that primary level centers are not equipped to diagnose or manage, leading to suboptimal outcomes. Knowledge of common alternative diagnoses is essential to inform facilitated referral for common mimicking disorders in children.

Journal ArticleDOI
TL;DR: A comprehensive understanding of role of CD3dim/CD56+ NKT in antimycobacterial immunity may enable new possibilities for NK cell-based prophylactic and/or therapeutic strategies against TB.
Abstract: Background: Tuberculosis (TB) control is challenging due to poor drug compliance and emerging resistance. The need of the hour is to determine the prediction of disease cure and relapse. Patients' immune response is crucial to the disease outcome. This study was designed to study the immune profile of TB patients during treatment and cure. Methods: The cross-sectional study included newly diagnosed pulmonary TB patients and healthy controls. Levels of serum cytokines/chemokines (Th1/Th2/Th17) were measured by BD cytometric bead array. The cell surface markers assessed in the study were CD3, CD4, CD8, CD16, CD56, and BD human regulatory T cell cocktail (CD4/CD25/CD127). Results: Data analysis observed statistically significant differences in CD3dim/CD56 + natural killer T (NKT) among TB patients with significantly low levels in healthy controls and after treatment completion (P

Journal ArticleDOI
TL;DR: The proposed variants improved the performance of the standard sputum smear, making it an important test for settings with high rates of smear-negative TB cases.
Abstract: Background: Direct sputum smear is still the first-choice tool for screening of tuberculosis worldwide. Variants of this technique, to improve the sensitivity are desired. Methods: Two microbiological variants of the standard sputum smear (”pellet” and “diluted-pellet”) for both Ziehl-Neelsen (ZN) and auramine fluorescence (AF) staining were evaluated. In addition, two methods for concentration of mycobacteria in sputum, using positive and negative pressure filtration, were tested and compared. The evaluation of the microbiological variants was performed on 98 culture positive sputum samples from different TB patients. The diagnostics sensitivity and the level of detritus in the processed sputum were determined. Bacilli load in the smear variants was determined by microscopic observation and by manual inspection of microscopic digital images. The comparison of the mycobacteria filtration methods was performed on 76 smear positive sputum samples. Filters retaining the concentrated mycobacteria were stained with AF and compared with the direct smear. Bacilli load, detritus level, filtered volume, filtration time and background noise level, were determined. Results: The sensitivity of microscopy with the microbiological variants was 7.1% and 2% higher in ZN and AF respectively, compared to direct smear. The sensitivity of AF in diluted pellet was significantly higher than all ZN variants (P

Journal ArticleDOI
TL;DR: The species diversity of NTM found in the setting suggests the importance of the use of new modern methods for accurate identification of N TM at species level and in some case at subspecies level for the proper treatment and management of patients.
Abstract: Background: Nontuberculous mycobacteria (NTM) have been identified in human pulmonary and extrapulmonary infections and are increasing globally, which makes it challenging to identify them. This article reports our experience with the laboratory identification of NTM in clinical practice among pulmonary and extrapulmonary samples received in our routine work. Methods: The study was conducted at the Universite Catholique de Louvain at the Cliniques Universitaires Saint-Luc, Brussels, Belgium, from 2015 to 2018. A total of 386 clinical samples were collected from patients suspected of having pulmonary or extrapulmonary mycobacterial infections. Routine laboratory methods phenotypic and molecular tests were performed. Results: The majority of NTM species were isolated from pulmonary samples (68%). The most prevalent species identified were Mycobacterium chimaera_intracellulare group (32%), followed by Mycobacterium avium complex (21%), Mycobacterium abscessus complex (18%), Mycobacterium gordonae (9%), and Mycobacterium chelonae (4%). In extrapulmonary samples, M. avium and M. chimaera_intracellulare were the most frequently isolated. Conclusion: The species diversity of NTM found in our setting suggests the importance of the use of new modern methods for accurate identification of NTM at species level and in some case at subspecies level for the proper treatment and management of patients.

Journal ArticleDOI
TL;DR: Standard treatment for patients with NDPTB is considered successful in case of faster health improvement and stabilization, less pronounced rates of toxic adverse reactions to antiTB drugs, faster sputum smear and culture conversion and cavity healing, signs of clinical and radiological convalescence, and the reduced number of large residual changes after the treatment compared with RTB.
Abstract: Background: To study the effectiveness of antituberculosis chemotherapy in patients with relapse pulmonary tuberculosis (RTB) compared with patients with the newly diagnosed process. Methods: We examined 285 TB patients, including 126 individuals with RTB (Group 1) and 159 patients with newly diagnosed pulmonary tuberculosis (NDPTB) (Group 2). All patients were diagnosed with infiltrative PTB. Effectiveness of the basic course of antimycobacterial treatment was assessed in accordance with the following data: time required for the normalization of clinical manifestations, smear conversion, cavity healing, disappearance of infiltrative and focal changes in the pulmonary tissue, as well as the final clinical effectiveness of therapy. Results: Disappearance of clinical symptoms was statistically significantly faster in Group 2 compared with RTB patients in 2.25 ± 0.11 and 3.40 ± 0.15 months, respectively (P

Journal ArticleDOI
TL;DR: A case of Type 1 downgrading reaction in which multidrug resistance was the probable cause of steroid-nonresponsiveness and which responded promptly on starting alternate antileprosy treatment is presented.
Abstract: While Type 1 reaction in Hansen's disease is commonly encountered, the triggers and reasons for its persistence are not well understood even though the immunological milieu and cytokine interplay have been studied. Herein, we present a case of Type 1 downgrading reaction in which multidrug resistance was the probable cause of steroid-nonresponsiveness and which responded promptly on starting alternate antileprosy treatment.

Journal ArticleDOI
TL;DR: The uncommonness of the skin involvement in TB infection should warn the clinicians to commit every possible examination to detect the TB involvement in other organs, especially in immunocompromised children with suspected skin lesions.
Abstract: Multifocal tuberculosis (TB) is rare. The risk of occurrence of multifocal TB is increasing in immunocompromised patients. Cutaneous entanglement in multifocal TB occurs more infrequently, and its association with multifocal TB is scarcely reported. The aim of this case report was to show a rare case of lupus vulgaris accompanied by multifocal skeletal TB (vertebrae and knee joint) in a 15-year-old girl. There were kyphosis and deformities seen on physical examination. Dermatological status showed an erythematous plaque on the cheek and an erythematous nodule on the index finger of the left hand. The additional examinations such as bacteriological, histopathological, and polymerase chain reaction (PCR) examinations supported the diagnosis of cutaneous TB. Radiographic and PCR examinations confirmed the diagnosis of multiple skeletal TB. Mycobacterium tuberculosis was obtained from GeneXpert® examination of the skin lesion on the right cheek and synovial fluid of the knee. Therefore, multifocal TB could be confirmed in this patient. The uncommonness of the skin involvement in TB infection should warn the clinicians to commit every possible examination to detect the TB involvement in other organs, especially in immunocompromised children with suspected skin lesions.

Journal ArticleDOI
TL;DR: Investigation of a new algorithm for diagnosis and treatment of tuberculosis (TB) related sepsis among PLHIV presenting with life-threatening illness increased TB case detection in patients that could have been missed by Xpert MTB/RIF assay.
Abstract: Background: Despite effort to diagnose tuberculosis (TB) in the Human Immunodeficiency Virus (HIV) infected population, 45% of adults with HIV that had a previously unknown reason for death, demonstrated TB was the cause by autopsy examination. We aimed to assess the clinical outcomes of implementation a new algorithm for diagnosis and treatment of tuberculosis (TB) related sepsis among PLHIV presenting with life-threatening illness. Methods: This study is a prospective cohort conducted in three-referral hospitals in Kilimanjaro, recruited 97 PLHIV from February through June 2018. Patients provided urine and sputum samples for testing lateral flow – lipoarabinomannan (LF-LAM) and Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) assays, respectively. Anti-TB was prescribed to patients with positive LF-LAM or Xpert MTB/RIF or received broad-spectrum antibiotics but deteriorated. Results: Of 97 patients, 84 (87%) provided urine and sputa, and 13 (13%) provided only urine. The mean age (95% confidence interval) was 40 (38–43) years and 52 (54%) were female. In 84 patients, LF-LAM increased TB detection from 26 (31%) by Xpert MTB/RIF to 41 (55%) by both tests. Of 97 patients, 69 (71%) prescribed anti-TB, 67% (46/69) and 33% (23/69) had definitive and probable TB respectively. Sixteen (16.5%) patients died, of which one died before treatment, 73% (11/15) died within 7 days of admission. The 30-day survival was similar in both treatment groups (log rank = 0.1574). Mortality was significantly higher among hospitalized patients compared to outpatients (P ≤ 0.027). Conclusion: Implementation of new algorithm increased TB case detection in patients that could have been missed by Xpert MTB/RIF assay. Survival of PLHIV with confirmed or probable TB was comparable to those of PLHIV that were treated with broad-spectrum antibiotics alone. Further work should focus on the optimal timing and content of the immediate antimicrobial regimen for sepsis among PLHIV in TB-endemic settings.

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TL;DR: A case of Histoid Hansen's disease with initial presentation of ENL while undergoing management for infertility is reported and is reported to be rare in this form of leprosy.
Abstract: Hansen's disease is a chronic infectious granulomatous disease with varied clinical presentation. Histoid Hansen's disease is an important emerging lepromatous subset of Hansen's disease known to mimic varied dermatoses. Occurrence of reactions, especially erythema nodosum leprosum (ENL), is rare in this form of leprosy. We report a case of Histoid Hansen's disease with initial presentation of ENL while undergoing management for infertility.

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TL;DR: This is a case report of a rare form of ET in a patient presenting with dysphagia, subjected to upper GI endoscopy, which revealed an ulcerative growth in the distal esophagus and Histopathology revealed ET.
Abstract: After a steady decline throughout the 20th century, the incidence of tuberculosis (TB) in industrialized countries has started to rise again. However, in developing countries like India, the menace of TB had never been controlled. Gastrointestinal (GI) TB is rare, and the GI tract is considered only the sixth most frequent site of extrapulmonary TB. Esophageal TB (ET) is still rarer. This is a case report of a rare form of ET in a patient presenting with dysphagia. The patient was subjected to upper GI endoscopy, which revealed an ulcerative growth in the distal esophagus. Histopathology revealed ET. The patient was managed conservatively with anti-TB treatment (ATT). In spite of the rare nature of the disease, it can be managed effectively with ATT to avoid complications (fistula, stricture, and esophageal perforation), which might warrant surgery.

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TL;DR: On performing in silico docking, it was found that neobavaisoflavone has better binding affinity than dapsone and forms a stable protein–ligand complex.
Abstract: Background: Leprosy is a neglected tropical disease affecting millions of people. The current treatment against leprosy includes various antibacterial drugs of which dapsone is known to bind to dihydropteroate synthase of Mycobacterium leprae. Dapsone is an expensive antibacterial drug with many side effects. A natural alternative for dapsone having less to no side effects and cheaper in production is needed. The three-dimensional protein structure of dihydropteroate synthase of M. leprae is not available. Methods: Protein homology modeling of target protein was carried out, and protein structure validation and energy minimization were performed. Phytochemicals mentioned in literature having anti-leprosy properties were studied for absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties and that which passed ADMET filters were further carried for comparative in silico docking analysis along with dapsone. Preliminary docking analysis was carried using AutoDock Vina, and results obtained were validated using AutoDock 4.2.6 and SwissDock. Results: Neobavaisoflavone was predicted to be ten times safer for administration than dapsone. On performing in silico docking, it was found that neobavaisoflavone has better binding affinity than dapsone and forms a stable protein–ligand complex. Residues GLY.50, THR.88, and VAL.107 play an important role as binding site residues. Conclusion: Further, in vitro and in vivo experimental studies are required to confirm anti-leprosy properties of neobavaisoflavone over drug dapsone.

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TL;DR: A 78-year-old male who presented with upper gastrointestinal bleed and also had abdominal pain and pulsating abdominal mass and on evaluation was found to have tubercular AEF which was successfully repaired with surgery and the patient recovered with antitubercular therapy along with the surgery.
Abstract: Tubercular aortitis presenting as primary aortoenteric fistula (AEF) is a rare entity. We present a 78-year-old male who presented with upper gastrointestinal bleed and also had abdominal pain and pulsating abdominal mass and on evaluation was found to have tubercular AEF which was successfully repaired with surgery and the patient recovered with antitubercular therapy along with the surgery. This case highlights the importance of high index of suspicion with early institution of surgical repair along with antitubercular therapy for tubercular AEF with good results.

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TL;DR: Tuberculous abscess of longissimus muscle in a young immunocompetent female is presented, and TB should be considered in the differential diagnosis of any unexplained soft-tissue swelling in people born in tubercular endemic areas.
Abstract: Muscle's tuberculosis (TB) without coexistent active skeletal involvement is very rare. We presented a case of tuberculous abscess of longissimus muscle in a young immunocompetent female. Magnetic resonance imaging showed a well-circumscribed lesion in the longissimus muscle. No bony abnormality was noticed. An ultrasound-guided biopsy revealed the presence of granulomatous features on cytological pathology. A good response was seen with antitubercular treatment. TB should be considered in the differential diagnosis of any unexplained soft-tissue swelling in people born in tubercular endemic areas. To the best of our knowledge, our observation is the third reported case in immunocompetent patient.

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TL;DR: It is concluded that changes of cytokines that observed during the treatment of TB patients play a very important role in monitoring pulmonary TB and can be suitable biomarkers to assess the effectiveness of anti-TB therapy in patients with TB.
Abstract: Background: Human tuberculosis is a chronic inflammatory disease caused by mycobacterium tuberculosis. Pulmonary tuberculosis is the result of the failure of host immune system to control mycobacterium tuberculosis. The aim of the study was to asses the changes of the cytokines in active pulmonary tuberculosis patients before and after the use of anti-TB therapy. Methods: Multiple cytokine responses in active tuberculosis (TB) patients were investigated in this study following anti-TB drug therapy after 2 months. Ninety-six participants with pulmonary TB were engaged in the study between May 2018 and October 2018. Samples of blood were taken early before treatment at 0 and 2 months after using anti-TB therapy. The levels of interferon-gamma (IFN)-γ, interleukin-4 (IL-4), IL-6, IL-10, and tumor necrosis factor (TNF)-α in whole blood plasma collected from the QuantiFERON-TB Gold Plus were measured. Results: Compared with baseline levels, TNF-α, IL6 and IL10 were significantly lower following treatment whereas the IFN-γ and IL-4 increased significantly after treatment. The responses of five cytokines varied significantly after treatment (P